This invention relates to a squeeze bottle for dispensing a liquid, in particular a liquid medicament in a metered and substantially germ-free manner. In this invention, a squeeze bottle is to be understood as a container with a flexible wall, whereby by squeezing the container at the location of the flexible wall pressure is exerted to the contents of the container, whereby the contents are dispersed via a dispense opening.
In the art, squeeze bottles for dispensing a liquid in an unmetered sterile manner are known. In this respect, U.S. Pat. No. 5,154,325 describes a squeeze bottle having a duckbill valve, in which valve an antimicrobial component is present to keep dispensed liquid, remaining behind at the outer side of the valve, in sterile condition. Ventilation takes place via a sterile filter. A duckbill valve is to be understood as a tubular structure of flexible material, the end portion thereof defining an outflow opening, which opening is closed in rest position. This closed position is effected by a biased tension that is exerted by the tube wall at the location of the end portion in inner direction. The level of biased tension is dependent on the material chosen and can e.g. be increased by applying around the tube a fitting, optionally tapered ring-shaped element.
In U.S. Pat. No. 5,310,094 a squeeze bottle is described, wherein the dispense opening comprises two serially arranged duckbill valves. This construction prevents material that is dispensed from the last duckbill valve from flowing back into the container. The above-described squeeze bottles are however not suitable for dispensing in a metered manner.
Dosing devices for dispensing under metered conditions are also known. In U.S. Pat. No. 3,910,467 a tube for dispensing pasty material in a metered manner is described. The tube contains a metering chamber with a valve, which valve is partly in contact with the outer environment. By pressure on the tube the valve is opened, whereby a portion of the contents of the metering chamber is dispensed. During opening of the valve, the valve portion, which in closed condition of the valve is in contact with the outer environment in a non sterile manner, comes into contact with the contents of the metering chamber, whereby dispensing in a sterile manner is not guaranteed. In the device, described in DE-C-4310019, wherein a squeeze bottle is described with a metering chamber and a dispensing opening that can be closed by a valve, the valve is, in its closed position, in its entirety located in the metering chamber that is filled with liquid. By pressure on the squeeze bottle a major portion of the valve is moved from the metering chamber into the outer environment, resulting in a high risk of contamination. This device is therefore not suitable for dispensing in a sterile manner as well. In U.S. Pat. No. 4,376,495 a tube is described, wherein the volume of a metering chamber is adjusted with the aid of a needle-shaped element, accommodated in a screw cap, which element, in closed condition, contacts the material to be dispensed, present in the metering chamber. For dispensing, the cap is removed and the needle-shaped element is in contact with the environment. At reclosure of the device, there is a substantial risk of contamination. Also in EP-A-0 701 108 a metering device for liquids is described, wherein the liquid is dispensed from a stock container via a metering chamber. The volume of the metering chamber can be adjusted by means that come into contact with both the air from the environment as well as with the metering chamber, resulting in dispensing in a sterile manner being impossible from this device.
Further, numerous containers having fixed walls for dispensing liquids in a metered and a germ-free manner are known; such containers are for this purpose moreover provided with complicatedly engineered pumping devices. Actuating such devices therefore takes place by depressing a pumping element, and not by squeezing the walls of the container, like a squeeze bottle. Examples of metering pumps for dispensing a liquid in a metered way are described in e.g. EP-B-0 473 892, of which parts of the pump, that contact the liquid to be dispensed, such as the dispensing passage or the walls of the metering chamber, comprise an oligodynamic agent. In U.S. Pat. No. 5,253,788 a combination of a squeeze bottle and a pump containing a metering chamber is described. The metering chamber of this squeeze bottle is in communication, via a non-return valve, with a storage chamber containing a cosmetic preparation. By squeezing the squeeze bottle, the valve is opened, and the preparation can then flow into the metering chamber. To dispense the contents of the metering chamber to the environment, it is necessary to depress an actuating component; during this movement, the abovementioned non-return valve is closed, so that it is impossible for any material to flow back out of the metering chamber into the storage chamber. Therefore, two separate movements have to be carried out in order to meter and dispense a metered unit from the said squeeze bottle, namely squeezing the squeeze bottle and depressing the actuating component.
In the art, there is however a great need for a squeeze bottle for dispensing liquid in a metered and substantially germ-free manner. The advantage of a squeeze bottle is the simple actuation thereof and the possibility for cheap production on an industrial scale.
The invention therefore provides a squeeze bottle for dispensing a liquid, in particular a liquid medicament, in a metered and substantially germ-free manner, at least comprising:
a storage chamber for accommodating the liquid,
a metering chamber with a variable volume for dispensing from this chamber, under reduction of volume of the chamber, a measured volume of liquid,
restoring means for returning the metering chamber to its original state after a volume of liquid has been dispensed,
an inlet for placing the metering chamber in communication with the storage chamber by mediation of a flow restrictor, which flow restrictor counteracts flow from the metering chamber to the storage chamber substantially completely and, when the pressure in the storage chamber is increased, counteracts flow between the storage chamber and the metering chamber substantially completely and, when the increased pressure in the storage chamber is removed, allows flow from the storage chamber into the metering chamber,
at least one outflow opening for placing the interior of the metering chamber in communication with the environment, the outflow opening comprising a non-return valve, which exclusively allows flow in the intended dispense direction, the valve being designed in such a way that valve portions that are, in closed position, in direct contact with the environment, are also located outside the metering chamber in opened position of the valve, and valve portions that are, in opened position, in direct contact with the environment, are also located outside the metering chamber in closed position of the valve,
actuating means for reducing the volume of the metering chamber, which actuating means can be actuated by squeezing the bottle,
means for ventilating the squeeze bottle.
In the context of this application, germ-free conditions are also understood to mean low-germ conditions, which term is defined in the European Pharmacopoeia (3rd edition).
Germs are to be understood as all biologically multipliable life forms, comprising e.g. bacteria, spores of bacteria, fungi, yeast cells etc.
By applying pressure to the storage chamber by squeezing the wall of the squeeze bottle an increased pressure is exerted on the metering chamber. This increased pressure reduces the volume of the metering chamber, for example by a partition between the storage chamber and the metering chamber, on which the said increased pressure is exerted, being at least partially depressed. As a result of the reduction in volume of the metering chamber, the valve will be opened at the location of the outlet and the contents of the metering chamber will be dispensed, while feed from the storage chamber as well as dispensing to the storage chamber, is substantially blocked.
As soon as the pressure on the tock chamber is removed, the metering chamber is forced back into the original state, for example spring means. When this increase in the volume of the metering chamber takes place, the flow restrictor allows flow to take place from the storage chamber to the metering chamber, so that the metering chamber is filled with material to be dispensed. The material which is situated in the metering chamber is dispensed by increasing the pressure on the storage chamber, as has been explained above.
By the fact that the outflow opening comprises a non-return valve, it is prevented that after dispensing, a passage in the squeeze bottle remains filled with liquid, which liquid will be dispensed in the next metering action, and remains, until said action, in contact with the environment and susceptible to contamination. To counteract contamination, the valve in the squeeze bottle according to the invention is furthermore designed in such a way, that the valve portions that come into contact with the metering chamber do not come in contact with the outer environment and vice versa, so that contamination or fouling of the liquid in the metering chamber via the non-return valve is virtually excluded.
During ventilation of the squeeze bottle according to the invention it is to be prevented that the contents of the bottle come into contact with germs from the air resulting into contamination.
The ventilating means in the squeeze bottle according to the invention can e.g. be designed as a sterile hydrophobic filter that can be accommodated in or at the vicinity of the bottom of the squeeze bottle wall. In order to prevent leakage through the filter when the squeeze bottle is squeezed, the ventilating means may comprise a non-return valve at the inside of the squeeze bottle, which valve is opened at ventilation of the storage chamber, and is closed in relaxed position of the squeeze bottle or during squeezing thereof. Such sterile ventilation means are generally known in the art, see e.g. WO 94/11115. When a filter is applied, the openings thereof are preferably maximally 0,2 xcexcm.
The ventilating means may also comprise an opening in the wall of the squeeeze bottle, wherein the liquid in the storage chamber is accommodated in a bag of flexible material, which bag is connected in a sealed manner with the metering chamber. In this way the air, taken up in the storage chamber during ventilation cannot come into contact with the liquid. Suitable materials for the bag which may be mentioned are optionally organic additives comprising thermoplastic materials, or a laminate of thermoplastic materials with high. gas barrier properties.
Thus, as a result of squeezing the squeeze bottle, material is dispensed from the metering chamber in a sterile way and the metering chamber is filled again after squeezing, i.e. when the squeeze bottle regains its original volume.
Further embodiments of the squeeze bottle according to the invention are explained in the subclaims.